This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 1 diabetes T1D is still associated with tremendous morbidity and premature mortality. Patients require multiple daily insulin injections throughout their lives as well as close monitoring of their diet and blood sugar levels to prevent complications. Unfortunately, there is presently no permanent cure for diabetes. Whole pancreas or islet cell transplantation is available only to a very limited number of patients and necessitates potential lifelong immunosuppressive therapy. Rituximab RITUXAN, Genentech and Biogen Idec is a chimeric murine/human monoclonal antibody approved for the treatment of B cell non-Hodgkins lymphoma. The antibody binds to the CD20 antigen on the surface of B cells and mediates B cell depletion. This study is a two-arm, multicenter, randomized, doublemasked, placebo-controlled clinical trial of Rituximab in patients with new onset Type 1 diabetes. Both groups will receive standard intensive diabetes treatment with insulin and dietary management. The objective of this study is to assess the safety, efficacy, and mode of action of rituximab, anti-CD20 monoclonal antibody, for the treatment of individuals with new onset type 1 diabetes.